Method of Manufacturing a Diagnostic Test Strip

ABSTRACT

A method for manufacturing a biosensor is provided. The method may include positioning a shadow mask containing a pattern of a plurality of feature sets over a substantially planar base layer containing a plurality of registration points. The method may also include forming at least one of the plurality of feature sets on the substantially planar base layer by selectively depositing a layer of a conductive material on the substantially planar base layer by passing the conductive material through the pattern of the shadow mask and removing the shadow mask from the substantially planar base layer. Alternatively, the method may include providing a laminate structure including a substantially planar base layer containing a plurality of registration points and a photoresist layer containing a pattern of a plurality of feature sets. The method may further include forming at least one of the plurality of feature sets on the substantially planar base layer by selectively depositing a layer of a conductive material on the substantially planar base layer by passing the conductive material through the pattern of the photoresist layer and removing the photoresist layer from the substantially planar base layer.

TECHNICAL FIELD

The present invention relates to the field of diagnostic testing and,more particularly, to diagnostic testing systems using electronicmeters.

BACKGROUND

Electronic testing systems are commonly used to measure or identify oneor more analytes in a sample. Such testing systems can be used toevaluate medical samples for diagnostic purposes and to test variousnon-medical samples. For example, medical diagnostic meters can provideinformation regarding the presence, amount, or concentration of variousanalytes in human or animal body fluids. In addition, diagnostic testmeters can be used to monitor analytes or chemical parameters innon-medical samples such as water, soil, sewage, sand, air, beverage andfood products or any other suitable sample.

Diagnostic testing systems typically include both test media, such asdiagnostic test strips, and a test meter configured for use with thetest media. Suitable test media may include a combination of electrical,chemical, and/or optical components configured to provide a responseindicative of the presence or concentration of an analyte to bemeasured. For example, some glucose test strips include electrochemicalcomponents, such as glucose specific enzymes, buffers, and one or moreelectrodes. The glucose specific enzymes may react with glucose in asample, thereby producing an electrical signal that can be measured withthe one or more electrodes. The test meter can then convert theelectrical signal into a glucose test result.

There is a demand for improved test media. For example, in the bloodglucose testing market, consumers consistently insist on test media thatrequire smaller sample sizes, thereby minimizing the amount of bloodneeded for frequent testing. Consumers also demand robust performanceand accurate results, and will not tolerate erroneous tests due toinadequate sample size. In addition, in all diagnostic testing markets,consumers prefer faster, cheaper, more durable, and more reliabletesting systems.

Current methods of manufacturing diagnostic test media have inherentlimits. For example, current methods for producing test media electrodesand depositing enzymes or other chemicals may have limited spatialresolution and/or production speeds. Furthermore, some productionprocesses cannot be used to deposit some enzymes, chemicals, andelectrodes. In addition, some production processes may be used toproduce or deposit some test media components, such as electrodes orenzymes, while being incompatible with other components. Therefore, sometest media production processes may require multiple productiontechniques, thereby increasing production cost and time, and decreasingproduct throughput.

Several methods for manufacturing biosensors have been proposed. Onesuch method is described in U.S. Pat. No. 6,875,327 to Miyazaki et al.Miyazaki et al. describe a biosensor manufacturing process whereby aconductive layer is formed on a support. Electrodes are formed using alaser to form multiple “slits” in the conductive layer, which formelectrical separations between the working, counter and detectingelectrodes. Following electrode formation, chemical reagents areselectively applied to the conductive layer.

U.S. Pat. No. 6,805,780 to Ryu et al. describes a method for producingelectrochemical biosensor test strips. The process includes forming agroove in a first insulating substrate and sputtering a metal onto theinsulating substrate with the aid of a shadow mask to form a pair ofelectrodes. The shadow mask should be in close contact with thesubstrate to avoid deposited material entering gaps and reducing thequality of the pattern formed. The shadow mask may be placed in contactwith a substrate, or may be formed by cutting a pattern in a plasticlayer adhered to the substrate, which is termed “adhesive-type shadowmask.”

U.S. Published Application No. 2005/0161826 to Shah et al. describes amanufacturing method that utilizes shadow mask techniques and lift-offlithography. Lift-off lithography uses a photo-resist layer patterned toform a negative image of the conducting elements. A thin metal film isformed over the substrate by, for example, sputtering. Next, thephoto-resist layer is removed by chemical stripping, leaving conductiveelements formed by the metal that remains on the substrate. The shadowmask process is also used to form sacrificial structures on thesubstrate, and multiple layers of dielectric and conductor material maybe formed using both processes. Initially a dielectric substrate base isformed, followed by patterning a blanket layer of conductive thin-film.Sacrificial structures may then be formed, using, shadow maskdeposition. At least one dielectric layer is deposited on the multilayercircuit. Conductors and sacrificial structures may then be created andremoved, forming multiple conductive and dielectric layers.

There exists the need to mass-produce biosensors cost effectively andwith high precision. The prior art references have several limitationssolved by the current invention. Although the electrode design describedby Miyazaki et al. can provide a functional biosensor, improved methodsof manufacturing biosensor electrodes are desirable. Specifically, othermanufacturing methods may be used to lower the cost and/or increase thequality of electrode formation and biosensor performance. For example,steps described by Rye et al. may require the formation of a groove inthe substrate, adding cost and complexity to biosensor manufacturing.Further, Rye et al. discloses the formation of a single test stripcontaining only two electrodes. Other limitations of the prior artinclude the fact that Shah et al. requires the application of at leastone dielectric layer to form the multilayer circuit structure.

Accordingly, there is a need for improved methods of manufacturingdiagnostic testing systems.

SUMMARY

A first aspect of the present invention includes a method formanufacturing a test strip. The method includes positioning a shadowmask containing a pattern of a plurality of feature sets over asubstantially planar base layer containing a plurality of registrationpoints. The method also includes forming at least one of the pluralityof feature sets on the substantially planar base layer by selectivelydepositing a layer of a conductive material on the substantially planarbase layer by passing the conductive material through the pattern of theshadow mask and removing the shadow mask from the substantially planarbase layer.

A second aspect of the present invention includes a method formanufacturing a test strip. The method includes providing a laminatestructure including a substantially planar base layer containing aplurality of registration points and a photoresist layer containing apattern of a plurality of feature sets. The method also includes formingat least one of the plurality of feature sets on the substantiallyplanar base layer by selectively depositing a layer of a conductivematerial on the substantially planar base layer by passing theconductive material through the pattern of the photoresist layer andremoving the photoresist layer from the substantially planar base layer.

Additional aspects and advantages of the invention will be set forth inpart in the description which follows, and in part will be apparent fromthe description, or can be learned by practice of the invention. Theadvantages of the invention will be realized and attained by means ofthe elements and combinations particularly pointed out in the appendedclaims.

It is to be understood that both the foregoing general description andthe following detailed description are exemplary and explanatory onlyand are not restrictive of the invention, as claimed.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are incorporated in and constitute apart of this specification, illustrate several embodiments of theinvention and together with the description, serve to explain theprinciples of the invention.

FIG. 1A illustrates test media that can be produced using the methods ofthe present disclosure.

FIG. 1B illustrates a test meter that can be used with test mediaproduced according to the methods of the present disclosure.

FIG. 1C illustrates a test meter that can be used with test mediaproduced according to the methods of the present disclosure.

FIG. 2A is a top plan view of a test strip according to an exemplaryembodiment of the invention.

FIG. 2B is a cross-sectional view of the test strip of FIG. 2A, takenalong line 2B-2B.

FIG. 3A is a top view of a reel according to an exemplary disclosedembodiment of the invention.

FIG. 3B is an enlarged tip view of a feature set on the reel of FIG. 3A.

FIG. 4A is a cross-sectional view and a top view of a structure thatillustrate a method for manufacturing a test strip using a lift-offlithography process, according to an exemplary disclosed embodiment.

FIG. 4B is a cross-sectional view and a top view of the structure ofFIG. 4A illustrating a method for manufacturing the test strip usinglift-off lithography process, according to the exemplary disclosedembodiment.

FIG. 4C is a cross-sectional view and a top view of the structure ofFIG. 4B illustrating a method for manufacturing the test strip usinglift-off lithography process, according to the exemplary disclosedembodiment.

FIG. 4D is an enlarged view of a cross-section of the structure shown byFIGS. 4B and 4C, illustrating a method for manufacturing the test stripusing lift-off lithography process, according to the exemplary disclosedembodiment.

FIG. 4E is an enlarged view of a cross-section of the structure shown byFIGS. 4B and 4C, illustrating a method for manufacturing the test stripusing lift-off lithography process, according to the exemplary disclosedembodiment.

FIG. 5A is a cross-sectional view and a top view of a shadow mask,according to an exemplary disclosed embodiment.

FIG. 5B is a cross-sectional view and a top view of the shadow mask ofFIG. 5A illustrating a method for manufacturing a test strip using theshadow mask, according to an exemplary disclosed embodiment.

FIG. 5C is a cross-sectional view and a top view of the structure ofFIG. 5B illustrating a method for manufacturing the test strip using theshadow mask, according to an exemplary disclosed embodiment.

FIG. 6 is a top view of a conductive base layer of a test stripaccording to an exemplary embodiment of the invention.

FIG. 7 is a top view of a dielectric layer of a test strip according toan exemplary embodiment of the invention.

DESCRIPTION OF THE EMBODIMENTS

Reference will now be made in detail to the exemplary embodiments of theinvention, examples of which are illustrated in the accompanyingdrawings. Wherever possible, the same reference numbers will be usedthroughout the drawings to refer to the same or like parts.

In accordance with an exemplary embodiment, a biosensor manufacturingmethod is described. Many industries have a commercial need to monitorthe concentration of particular constituents in a fluid. The oilrefining industry, wineries, and the dairy industry are examples ofindustries where fluid testing is routine. In the health care field,people such as diabetics, for example, need to monitor variousconstituents within their bodily fluids using biosensors. A number ofsystems are available that allow people to test a body fluid (e.g.blood, urine, or saliva), to conveniently monitor the level of aparticular fluid constituent, such as, for example, cholesterol,proteins or glucose.

A biosensor may include a test strip, which can be disposable, that mayfacilitate the detection of a particular constituent of a body fluid.The test strip can include a proximal end, a distal end, and at leastone electrode. The proximal end of the test strip may include a samplechamber for receiving a body fluid to be tested. The sample chamber canbe dimensioned and configured to draw a fluid sample into the samplechamber via capillary action. Electrodes positioned within the samplechamber may contact the fluid sample. The distal end of the test stripmay be configured to operatively connect the test strip to a meter thatmay determine the concentration of the body fluid constituent. Forexample, the distal end of the test strip may include a plurality ofelectrical contacts configured to provide electrical connections betweenthe electrodes within the sample chamber and the meter. The ends of thetest strip may also include a visual and/or tactile distinguishablesection, such as, for example, a taper, in order to make it easier forthe user to operatively connect the test strip to the meter or apply abody fluid to the sample chamber.

Electrodes positioned within the sample chamber may include a workingelectrode, a counter electrode, and a fill-detect electrode. A reagentlayer can be disposed in the sample chamber and may cover at least aportion of the working electrode, which can also be disposed at leastpartially in the sample chamber. The reagent layer can include, forexample, an enzyme, such as glucose oxidase, and a mediator, such aspotassium ferricyanide or ruthenium hexamine, to facilitate thedetection of glucose in blood. It is contemplated that other reagentsand/or other mediators can be used to facilitate detection of glucoseand other constituents in blood and other body fluids. The reagent layercan also include other components, such as buffering materials (e.g.,potassium phosphate), polymeric binders (e.g.,hydroxypropyl-methyl-cellulose, sodium alginate, microcrystallinecellulose, polyethylene oxide, hydroxyethylcellulose, and/or polyvinylalcohol), and surfactants (e.g., Triton X-100 or Surfynol 485).

The present disclosure provides a method for producing a diagnostic teststrip 10, as shown in FIG. 1A. Test strip 10 of the present disclosuremay be used with a suitable test meter 200, 208, as shown in FIGS. 1Band 1C, to detect or measure the concentration of one or more analytes.The analytes to be tested for may include a variety of differentsubstances, which may be found in biological samples, such as blood,urine, tear drops, semen, feces, gastric fluid, sweat, cerebrospinalfluid, saliva, vaginal fluids (including suspected amniotic fluid),culture media, and/or any other biologic sample. The one or moreanalytes may also include substances found in environmental samples suchas soil, food products, ground water, pool water, and/or any othersuitable sample.

As shown in FIG. 1A, test strip 10 are planar and elongated in design.However, test strip 10 may be provided in any suitable form including,for example, ribbons, tubes, tabs, discs, or any other suitable form.Furthermore, test strip 10 can be configured for use with a variety ofsuitable testing modalities, including electrochemical tests,photochemical tests, electro-chemiluminescent tests, and/or any othersuitable testing modality.

Test meter 200, 208 may be selected from a variety of suitable testmeter types. For example, as shown in FIG. 1B, test meter 200 includes avial 202 configured to store one or more test strips 10. The operativecomponents of test meter 200 may be contained in a meter cap 204. Metercap 204 may contain electrical meter components, can be packaged withtest meter 200, and can be configured to close and/or seal vial 202.Alternatively, a test meter 208 can include a monitor unit separatedfrom storage vial, as shown in FIG. 1C. Any suitable test meter may beselected to provide a diagnostic test using test strip 10 producedaccording to the disclosed methods.

Test Strip Configuration

With reference to the drawings, FIGS. 2A and 2B show a test strip 10, inaccordance with an exemplary embodiment of the present invention. Teststrip 10 can take the form of a substantially flat strip that extendsfrom a proximal end 12 to a distal end 14. In one embodiment, theproximal end 12 of test strip 10 can be narrower than distal end 14 toprovide facile visual recognition of distal end 14. For example, teststrip 10 may include a tapered section 16, in which the full width oftest strip 10 tapers down to proximal end 12, making proximal end 12narrower than distal end 14. If, for example, a blood sample is appliedto an opening in proximal end 12 of test strip 10, providing taperedsection 16 and making proximal end 12 narrower than distal end 14 canassist the user in locating the opening where the blood sample is to beapplied. Alternatively, the distal end may be tapered. Further, othervisual means, such as indicia, notches, contours or the like can beused.

Test strip 10 is depicted in FIGS. 2A and 2B as including a plurality ofelectrodes 22, 24, 28, 30. Each electrode may extend substantially alongthe length of test strip 10 to provide an electrical contact near distalend 14 of test strip 10 and a conductive region electrically connectingthe region of the electrode near proximal end 12 to the electricalcontact. In the exemplary embodiment of FIGS. 2A and 2B, the pluralityof electrodes includes a working electrode 22, a counter electrode 24, afill-detect anode 28, and a fill-detect cathode 30 at a proximal end 12of test strip 10. Correspondingly, the electrical contacts can include aworking electrode contact 32, a counter electrode contact 34, afill-detect anode contact 36, and a fill-detect cathode contact 38positioned at distal end 14 of test strip 10. The conductive regions mayinclude a working electrode conductive region 40 that electricallyconnects the proximal end of working electrode 22 to working electrodecontact 32, a counter electrode conductive region 42 that electricallyconnects the proximal end of counter electrode 24 to counter electrodecontact 34, a fill-detect anode conductive region 44 that electricallyconnects the proximal end of fill-detect anode 28 to fill-detect contact36, and a fill-detect cathode conductive region 46 that electricallyconnects the proximal end of fill-detect cathode 30 to fill-detectcathode contact 38.

In one embodiment, at least one electrode is partially housed within asample chamber to allow contact with a fluid to be tested. For example,FIG. 2B depicts test strip 10 as including a slot 52 that forms aportion of sample chamber 88 at proximal end 12. Slot 52 can define anexposed portion 54 of working electrode 22, an exposed portion 56 ofcounter electrode 24, an exposed portion 60 of fill-detect anode 28, andan exposed portion 62 of fill-detect cathode 30. Further, the exemplaryembodiment includes an auto-on conductor 48 disposed near distal end 14of strip 10 to allow the meter to determine that a test strip isoperatively connected to the meter.

As shown in FIG. 2B, test strip 10 may have a layered construction. Teststrip 10 includes a base layer 18 that may substantially extend alongthe entire length or define the length of test strip 10. Base layer 18can be formed from an electrically insulating material and can have athickness sufficient to provide structural support to test strip 10.

According to the exemplary embodiment of FIG. 2B, one or more conductivecomponents 20 may be disposed on at least a portion of base layer 18.Conductive components 20 may include one or more electrically conductiveelements, such as, for example, a plurality of electrodes. Conductivecomponents 20 may include any suitable conductive or semi-conductivematerial, such as, for example, gold, platinum, silver, iridium, carbon,indium tin oxide, indium zinc oxide, copper, aluminum, gallium, iron,mercury amalgams, tantalum, titanium, zirconium, nickel, osmium,rhenium, rhodium, palladium, an organometallic, or a metallic alloy.

Layered on top of base layer 18 and conductive components 20 is a spacerlayer 64. Spacer layer 64 may include an electrically insulatingmaterial such as polyester. Spacer layer 64 can cover portions ofworking electrode 22, counter electrode 24, fill-detect anode 28,fill-detect cathode 30, and conductive regions 40-46. In the exemplaryembodiment of FIG. 2B spacer layer 64 does not cover electrical contacts32-38 or auto-on conductor 48. For example, spacer layer 64 can cover asubstantial portion of conductive components 20, from a line proximal ofcontacts 32 and 34 to proximal end 12, except for slot 52 extending fromproximal end 12.

A cover 72 may be provided. As shown in FIG. 2B, cover 72 may have aproximal end 74 and a distal end 76 and may be disposed at proximal end12 of test strip 10 to cover slot 52 thereby partially forming samplechamber 88. Cover 72 can be attached to spacer layer 64 via an adhesivelayer 78. Adhesive layer 78 can include a polyacrylic or other adhesiveand may include sections disposed on spacer layer 64 on opposite sidesof slot 52. In some embodiments, a break 84 in adhesive layer 78 mayextend from distal end 70 of slot 52 to an opening 86. It is alsocontemplated that cover 72 may include one or more openings (not shown)configured to permit venting of sample chamber 88. Cover 72 can bedisposed on adhesive layer 78 such that proximal end 74 of cover 72 maybe aligned with proximal end 12 and distal end 76 of cover 72 may bealigned with opening 86, thereby covering slot 52 and break 84. Cover 72may be composed of an electrically insulating material, such aspolyester. Additionally, cover 72 may be transparent.

Slot 52, together with base layer 18 and cover 72, may define samplechamber 88 in test strip 10, which receives a fluid sample, such as ablood sample, for measurement in the exemplary embodiment. A proximalend 68 of slot 52 can define a first opening in sample chamber 88,through which the fluid sample is introduced. At distal end 70 of slot52, break 84 can define a second opening in sample chamber 88, forventing sample chamber 88 as a fluid sample enters sample chamber 88.Slot 52 may be dimensioned such that a blood sample applied to itsproximal end 68 is drawn into and held in sample chamber 88 by capillaryaction, with break 84 venting sample chamber 88 through an opening 86,as the fluid sample enters. Moreover, slot 52 may be dimensioned so thatthe volume of fluid sample that enters sample chamber 88 by capillaryaction is about 1 micro-liter or less.

Test strip 10 may include one or more reagent layers 90 disposed insample chamber 88. In the exemplary embodiment, reagent layer 90contacts a partially exposed portion 54 of working electrode 22. It isalso contemplated that reagent layer 90 may or may not contact exposedportion 56 of counter electrode 24. Reagent layer 90 may includechemical components to enable the level of glucose or other analyte inthe body fluid, such as a blood sample, to be determinedelectro-chemically. For example, reagent layer 90 can include an enzymespecific for glucose, such as glucose oxidase or glucose dehydrogenase,and a mediator, such as potassium ferricyanide or ruthenium hexamine.Reagent layer 90 can also include other components, such as bufferingmaterials (e.g., potassium phosphate), polymeric binders (e.g.,hydroxypropyl-methyl-cellulose, sodium alginate, microcrystallinecellulose, polyethylene oxide, hydroxyethylcellulose, and/or polyvinylalcohol), and surfactants (e.g., Triton X-100 or Surfynol 485).

An example of the way in which chemical components of reagent layer 90may react with glucose in the blood is described next. The glucoseoxidase initiates a reaction that oxidizes glucose to gluconic acid andreduces the ferricyanide to ferrocyanide. When an appropriate voltage isapplied to working electrode 22, relative to counter electrode 24, theferrocyanide is oxidized to ferricyanide, thereby generating a currentthat is related to the glucose concentration in the blood sample.

As depicted in FIG. 2B, the position and dimensions of the layers oftest strip 10 may result in test strip 10 having regions of differentthicknesses. Of the layers above base layer 18, the thickness of spacerlayer 64 may constitute a substantial thickness of test strip 10. Thusthe distal end of spacer layer 64 may form a shoulder 92 in test strip10. Shoulder 92 may delineate a thin section 94 of test strip 10extending from shoulder 92 to distal end 14, and a thick section 96 oftest strip 10 extending from shoulder 92 to proximal end 12. Theelements of test strip 10 used to electrically connect it to test meter200, 208, namely, electrical contacts 32-38 and auto-on conductor 48,can all be located in thin section 94. Accordingly, test meter 200, 208can be sized and configured to receive thin section 94 but not thicksection 96. This may allow the user to insert the correct end of teststrip 10, i.e., distal end 14 of thin section 94, and can prevent theuser from inserting the wrong end, i.e., proximal end 12 of thicksection 96, into test meter 200, 208.

Test strip 10 can be sized for easy handling. For example, test strip 10may measure approximately 35 mm long (i.e., from proximal end 12 todistal end 14) and about 9 mm wide. According to the exemplaryembodiment, base layer 18 may be a polyester material about 0.35 mmthick and spacer layer 64 may be about 0.127 mm thick and cover portionsof working electrode 22. Adhesive layer 78 may include a polyacrylic orother adhesive and have a thickness of about 0.013 mm. Cover 72 may becomposed of an electrically insulating material, such as polyester, andcan have a thickness of about 0.1 mm. Sample chamber 88 can bedimensioned so that the volume of fluid sample held is about 1micro-liter or less. For example, slot 52 can have a length (i.e., fromproximal end 12 to distal end 70) of about 3.56 mm, a width of about1.52 mm, and a height (which can be substantially defined by thethickness of spacer layer 64) of about 0.13 mm. The dimensions of teststrip 10 for suitable use can be readily determined by one of ordinaryskill in the art. For example, a meter with automated test striphandling may utilize a test strip smaller than 9 mm wide.

Although FIGS. 2A and 2B show an exemplary embodiment of test strip 10,other configurations, chemical compositions and electrode arrangementscould be used. Different arrangements of working electrode 22, counterelectrode 24, fill-detect anode 28, and/or fill-detect cathode can alsobe used. In the configuration shown in FIGS. 2A and 2B, workingelectrode 22 and counter electrode 24 are separated by boundariesaligned in the x-axis, perpendicular to the length of test strip 10 inthe y-axis. Alternatively, working electrode 22 and counter electrode 24can be separated by boundaries aligned in the y-axis, parallel to thelength of test strip 10. It is also contemplated that working electrode22 and counter electrode 24 may be aligned at any angle relative thelength of test strip 10.

Test Strip Array Configuration

FIG. 3A shows a top view of reel 100 according to an exemplary disclosedembodiment. The term “reel” as used herein applies to a material ofcontinuous indeterminate length or to sheets of material of determinatelength. In some embodiments, reel 100 may include base layer 118. Asdescribed below, an array of conductive components 120 may be depositedon base layer 118. Various layers may be added to base layer 118 to formtest strip 110 similar to that described in FIG. 2B. Test strips 110 maythen be separated from the array of test strips 110 formed on reel 100to produce multiple individual test strips 110.

A plurality of feature sets 80 may be formed on base layer 118, whereineach feature set 80 may include a plurality of conductive components 20,such as, for example, an electrode, a conductive region and an electrodecontact. Feature sets 80 may include any suitable conductive orsemi-conductive material. In some embodiments, feature sets 80 can beformed using lift-off lithography or shadow masking, as described below.

Following the formation of one or more feature sets 80 on base layer118, various layers may be added to base layer 118 and feature sets 80to form a laminate structure as shown in FIG. 2B. Then, individual teststrips 110 may be separated from reel 100 via a “singulation” process,wherein the outer shape of test strip 110 formed by the manufacturingprocess may be represented by the dotted line shown in FIGS. 3A and 3B.In some embodiments, a single feature set 80 may include conductivecomponents 20 of a single test strip 110. Although FIGS. 3A and 3B showsone configuration of feature set 80, it is understood that otherconfigurations of feature set 80 may be used to form test strip 110.

As shown in FIG. 3A, feature sets 80 may be arranged in two rows on reel100. In the exemplary embodiment depicted, proximal ends 112 of the tworows of feature sets 80 are in juxtaposition in the center of reel 100and distal ends 114 of feature sets 80 are arranged at the periphery ofreel 100. It is also contemplated that proximal ends 112 and distal ends114 of feature sets 80 can be arranged in the center of reel 100, anddistal ends 114 of two rows of feature sets 80 can be arranged in thecenter of reel 100. Further, the separation distance between featuresets 80 may be designed to permit a single cut to separate adjacentfeature sets 80 during a singulation process.

As shown in FIG. 3A, reel 100 includes a plurality of registrationpoints 102 at the distal end 114 of each test strip on reel 100.Registration points 102 may be used during one or more manufacturingprocesses to locate a feature of test strip 110 relative to reel 100.One or more manufacturing steps may require registration points 102 toensure precise alignment of laminate layers and/or other manufacturingprocesses, such as, for example, deposition of conductive components,mask alignment, reagent deposition, singulation, etc. For example,registration points 102 may be used during lamination to ensure thatspacer layer 64 is properly positioned over base layer 18 such that slot52 is positioned to adequately expose portions of electrodes 54, 56, 60,62 as shown in FIGS. 2A and 2B. Registration points 102 may also beutilized during chemistry deposition, singulation or any other processassociated with the formation of test strips 110.

Registration points 102 may include any suitable reference marks, suchas, for example, holes, notches, indentations, raised regions or anyother suitable reference indication known in the art. Registrationpoints 102 may be formed by any suitable manufacturing process, such as,for example, laser ablation, stamping, physical deformation, etching,drilling, printing, punching, scoring, heating, compression molding,etc. Further, registration points 102 may be formed at any stage duringthe formation and/or processing of reel 100. For example, registrationpoints 102 may be formed during the formation of base layer 118 whereinregistration points 102 may be formed at regular intervals along baselayer 118. In some embodiments, registration points 102 may be formedduring the formation of feature sets 80. In particular, registrationpoints 102 may be formed on base layer 118 prior to using lift-offlithography or shadow masking techniques to form feature sets 80 asdescribed below, wherein the position of feature sets 80 on base layer118 may be dependent upon the position of registration points 102 onbase layer 118. In some embodiments a visual system (not shown) may beused to ensure adequate positioning of the formation of feature sets 80relative to registration points 102. It is also contemplated thatadditional registration points 102 may be formed, such as, for example,a scribe line (not shown) that may be used during a subsequentmanufacturing process, such as, for example, singulation.

Registration points 102 may be located at any suitable location on reel100. As shown in FIG. 3A, registration points 102 may be locatedadjacent distal end 114 of each feature set 80. Registration points 102may also be located at positions other than distal end 114 of eachfeature set 80, such as, for example, adjacent to proximal end 112 offeature set 80. As feature sets 80 may be located on reel 100 in variouspatterns and various densities, so to may registration points 102 beappropriately located. For example, it may be appropriate to positionregistration points 102 between feature sets 80.

Registration point 102 may be distributed at any suitable density onreel 100. In addition, registration points 102 may be distributed onreel 100 at a density different than the density of feature sets 80 onreel 100. For example, the number of registration points 102 distributedwithin a select region of reel 100 may be different than the number offeature sets 80 distributed within the select region of reel 100. Insome embodiments, there may be one registration point for every featureset, and in other embodiments there may be one registration point forevery five, ten, or twenty features sets. It is also contemplated thatregistration points 102 may be separated by different distances ordistributed at different densities than feature sets 80 on reel 100. Thedistribution of feature sets 80 and/or registration points 102 maydepend on one or more characteristics of the manufacturing process usedto produce test strip 10 and/or the design of test strip 10.

Manufacturing of Test Strips

FIGS. 4A-4E illustrate a method for manufacturing a test strip 110 usinga lift-off lithography process, according to an exemplary disclosedembodiment. Lithography typically includes the formation of a pattern ina photosensitive material by the selective exposure of radiation to thepatterned region of the photosensitive material. Photosensitive materialmay include any suitable material that may change a property uponexposure to radiation, such as, visible light or ultra-violet radiation.Exposure of a photosensitive material to radiation can affect a propertyof the exposed and unexposed regions differently. For example, aproperty affected by radiation may include chemical resistance, whereinthe photosensitive material may be referred to as a photoresist. Aphotoresist material may exhibit differential resistance to chemicaletching whereby regions of the photoresist exposed to radiation may bedegraded by a chemical, and regions unexposed to radiation may resistchemical degradation. Such a process is known in the art and may be usedto form a photoresist patterned substrate 150 as shown in FIGS. 4A and4B. Specifically, a photoresist layer 148 may be formed on base layer118 using any suitable lithographic process known in the art.

Photoresist layer 148 may include any suitable photoresist material. Forexample, photoresist layer 148 may include Shipley's 1805™, Shipley's1813™, Shipley's 1818™, Shipley's 1045™, Shipley's 1075™, AZ's 9260™, orFuturex™. Other suitable materials may be used, and photoresist layer148 may be deposited on base layer 118 using any suitable method knownin the art.

Following deposition of photoresist layer 148 on base layer 118,lithography procedures can be used to produce a pattern 152 inphotoresist layer 148, as shown in FIG. 4A, wherein pattern 152 may forman array of feature sets 180, as shown in FIG. 4C. For example, a mask(not shown) containing pattern 152 may be placed over photoresist layer148. The mask and photoresist layer 148 may then be irradiated with UVlight to selectively alter a chemical property of the exposed region ofphotoresist layer 148. Alternatively, a laser (not shown) may be used toirradiate pattern 152 onto photoresist layer 148 such that no mask isrequired. Following selective exposure of photoresist layer 148 toradiation, a chemical may be applied to preferentially degrade exposedregions of photoresist layer 148 to form a photoresist patternedsubstrate 150.

Following formation of photoresist patterned substrate 150, a conductivematerial may be applied to photoresist patterned substrate 150 using aconductive material deposition method as shown in FIG. 4B. Conductivematerial may include any conductive or semi-conductive material, suchas, for example, palladium, gold, platinum, silver, iridium, carbon,indium tin oxide, indium zinc oxide, copper, aluminum, gallium, iron,mercury amalgams, tantalum, titanium, zirconium, nickel, osmium,rhenium, rhodium, palladium, an organometallic, or a metallic alloy.

Conductive material deposition methods may include any suitable method,such as, for example, physical vapor deposition, chemical vapordeposition, electroplating, or spray techniques. Physical vapordeposition may include sputtering, wherein vaporized ions of conductivematerial are directed onto photoresist patterned substrate 150. Physicalvapor deposition may also include evaporation, wherein a conductivematerial is heated in a vacuum to release particles that can condenseonto photoresist patterned substrate 150. Electroplating may includeplacing photoresist patterned substrate 150 in a liquid solution andapplying a potential to form conductive material on photoresistpatterned substrate 150. Spraying may include ultrasonic or pressurespraying and usually involves the deposition of a liquid form metal ink,typically an organometallic. The organic components may be sprayed ontophotoresist patterned substrate 150 to form a uniform conductive layer,and the substrate and conductive layer may be baked to remove organicsolvents and binders.

In some embodiments, a bonding layer (not shown) may be deposited onbase layer 118 before forming feature sets 180 on base layer 118. Inparticular, the bonding layer may be configured to enhance a bondstrength between base layer 118 and the conductive material by providingstronger adhesion between the conductive material and the bonding layerthan base layer 118 and the conductive material. For example, a bondinglayer of titanium or chromium may be deposited on base layer 118 beforedepositing the conductive material on base layer 118.

As shown in FIG. 4C, following a conductive material deposition process,photoresist layer 148 may be removed. Specifically, photoresist layer148 may be removed from base layer 118 by any suitable removal process,such as, for example, using a liquid or a gas solvent. Various solventsmay be used to remove photoresist layer 148, such as, for example, aShipley brand stripper, acetone, trichloroethylene, methyl ethyl ketone,or methyl isobutyl ketone. The removal of photoresist layer 148 maypreferentially remove photoresist layer 148 while not substantiallyremoving conductive material selectively deposited on base layer 118.Removal of photoresist layer 148 may expose conductive materialdeposited on base layer 118 through pattern 152, such as, for example,feature sets 80.

FIG. 4D illustrates an enlarged view of cross-sections of the structuresshown by FIGS. 4B and 4C, illustrating a method for manufacturing teststrip 110 using the lift-off lithography process. In some embodiments, awall feature 51 may be formed by a manufacturing process utilizinglift-off lithography and/or a shadow mask as described below. Wallfeature 51 may include an indentation or similar structure formed on thewall of one or more conductive components 120. For example, wall feature51 may include a shoulder or bevel at least partially extending along awall of conductive components 120.

One or more wall features 51 may result from a sputtering process. Inparticular, deposition of conductive material on base layer 118 throughphotoresist layer 148 may not result in complete deposition ofconductive material in regions adjacent to intersections between baselayer 118 and photoresist layer 148. For example, as shown in FIGS. 4Dand 4E, wall features 51′, 51″ may form at regions at the bottom ofconductive component 120 as conductive material deposited on base layer118 may not fill the entire region enclosed by photoresist 148.

In some embodiments, wall features 51 may be formed in any wall regionof conductive components 120. For example, as shown in FIGS. 4D and 4Ewall feature 51′″ may be formed at a top region of conductive component120. Wall feature 51′″ may be formed by sputtering conductive materialat a suitable trajectory toward photoresist patterned substrate 150, orany other method known in the art. It is also contemplated thatphotoresist layer 148 may include one or more structures representing amold of wall feature 51, such that conductive material may form in, oraround, the mold to form wall feature 51. For example, wall feature 51may include a protrusion in a wall of conductive components 120 formedby depositing conductive material in an indentation in a wall ofphotoresist layer 148.

FIGS. 5A-5C illustrate a method for test strip manufacturing using ashadow mask 50, according to an exemplary disclosed embodiment.Specifically, shadow mask 50 (see FIG. 5A) may be used to form one ormore feature sets 280 on base layer 218, wherein shadow mask 50 maycontain pattern 252 of feature sets 280. Shadow mask 50 may be producedby any method known in the art, such as, for example, by a photo-etchingprocess, an electroforming, or an etching process. Shadow mask 50 may bemade of any suitable material, such as, for example, molybdenum,aluminum, nickel, silicon or a polymer such as polyethyleneterephthalate. Shadow mask 50 may be placed over and maintained in closecontact with base layer 218 using any techniques known in the art.

As shown in FIG. 5A-5C, following suitable placement of shadow mask 50over base layer 218, a conductive material may be deposited on baselayer 218 as described previously with reference to FIGS. 4A-4C.Specifically, the conductive material may be deposited such thatconductive material may be formed on base layer 218 by passingconductive material through shadow mask 50. In particular, theconductive material may be deposited to form feature sets 280 by passingconductive material through pattern 252 of shadow mask 50.

As shown in FIG. 5C, shadow mask 50 may be removed from base layer 218following deposition of the conductive material. Shadow mask 50 may beremoved using methods known in the art, such as, for example, peelingshadow mask off base layer 218 or use of appropriate solvents. Followingremoval of shadow mask 50, reel 100 may be prepared for furthermanufacturing. As described above, it is also contemplated that featuresets 280 may include one or more wall features 51 (not shown). Wallfeatures 51 may arise from the deposition of conductive material on baselayer 218 passing through shadow mask 50, or may be formed if shadowmask 50 includes one or more structures representing a mold of wallfeature 51.

Shadow mask 50 and/or reel 100 may be configured to permit consistentproduction of high quality feature sets 280. In particular, shadow mask50 and/or reel 100 may be configured to permit formation of feature sets280 at a selected density and resolution. For example, shadow mask 50may be maintained in close contact with base layer 218 to minimize thelikelihood that deposited conductive material may flow between shadowmask 50 and base layer 218. In addition, shadow mask 50 may include anadhesive material (not shown), such as, for example, a pressuresensitive adhesive and/or a heat activated adhesive. The adhesivematerial may enhance the manufacturing process by providing removablebonding between shadow mask 50 and base layer 218. It is alsocontemplated that other methods may be used to maintain suitable contactbetween shadow mask 50 and base layer 218, such as, for example, use ofmagnets.

FIGS. 6 and 7 show a partially fabricated test strip structure 310 thatmay be fabricated according to the process described with respect toFIGS. 4A-4E and 5A-5C. In each of FIGS. 6 and 7, the outer shape of thetest strip 310 that would be formed in the overall manufacturing processis shown as a dotted line. Although these figures show steps formanufacturing test strip 310 with a configuration similar to that shownin FIGS. 1A, 2A, 2B, it is to be understood that similar steps can beused to manufacture test strips having other configurations ofcomponents.

As depicted in the exemplary embodiment shown in FIG. 6, test strip 310may include a plurality of conductive components 320, such as, forexample, electrodes 322, 324, 328 and 330. Conductive components 320 oftest strip 310 may be partially formed by forming feature set 380 asdiscussed above. In some embodiments, conductive components 320 may beat least partially formed by one or more processing techniques. Forexample, a processing technique, such as laser ablation, may be used tomore precisely define the boundaries of some conductive components 320.In other embodiments, a processing technique may include lamination,etching or a physical separation process, such as, for example, stampingand cutting.

Test strip 310 may also include one or more coding regions (not shown),configured to provide coding information on test strip 310. For example,coding regions may include a discrete set of contacting pads asdescribed in commonly-assigned, copending patent application “DIAGNOSTICSTRIP CODING SYSTEM AND RELATED METHODS OF USE”, filed Jul. 15, 2005(Attorney Docket 06882-0147), the disclosures of which is herebyincorporated herein by reference in its entirety. The discrete patternformed by a set of contacting pads may include conducting andnon-conducting regions designed to be readable by test meter to identifydata particular to the test strip.

Following the formation of feature set 380 on base layer 318, spacerlayer 364 can be applied to conductive components 320 and base layer318, as illustrated in FIG. 7. Spacer layer 364 can be applied toconductive components 320 and base layer 318 in a number of differentways. In an exemplary approach, spacer layer 364 may be provided as asheet or web large enough and appropriately shaped to cover multiplefeature sets 380. In this approach, the underside of spacer layer 364can be coated with an adhesive to facilitate attachment to conductivecomponents 320 and base layer 318. Various slots can be cut, formed orpunched out of spacer layer 364 to shape it before, during or after theapplication of spacer layer 364 to conductive components 320. Forexample, as shown in FIG. 7, spacer layer 364 can have a pre-formed slot352 for each test strip structure. Spacer layer 364 may be positionedover conductive components 320, as shown in FIG. 7, and laminated toconductive components 320 and base layer 318. When spacer layer 364 isappropriately positioned on conductive components 320, exposed electrodeportions 354-362 are accessible through slot 352. Similarly, spacerlayer 364 leaves contacts 332-338 and auto-on conductor 348 exposedafter lamination.

Alternatively, spacer layer 364 could be applied in other ways. Forexample, spacer layer 64 can be injection molded onto base layer 318 andconductive components 320. Spacer layer 64 could also be built up onbase layer 318 and conductive components 320 by screen-printingsuccessive layers of a dielectric material to an appropriate thickness,e.g., about 0.005 inches. An exemplary dielectric material comprises amixture of silicone and acrylic compounds, such as the “Membrane SwitchComposition 5018” available from E.I. DuPont de Nemours & Co.,Wilmington, Del. Other materials also could be used, however.

Reagent layer 390 (not shown) can then be applied to each test stripstructure after forming spacer layer 364. In an exemplary approach,reagent layer 390 may be applied by micro-pipetting an aqueouscomposition onto exposed portion 354 of working electrode 322 andletting it dry to form reagent layer 390. It is also contemplated thatreagent layer 390 may or may not contact exposed portion 356 of counterelectrode 324. An exemplary aqueous composition has a pH of about 7.5and contains 175 mM ruthenium hexamine, 75 mM potassium phosphate, 0.35%Methocel, 0.08% Triton X-100, 5000 u/mL glucose dehydrogenase, 5%sucrose, and 0.05% Silwet. Alternatively, other methods, such asscreen-printing, spray deposition, piezo and ink jet printing, can beused to apply the composition used to form reagent layer 390.

Cover 372 (not shown) can then be attached to spacer layer 364, wherecover 372 is constructed to cover slot 352, as previously described withrespect to FIG. 2B. In some embodiments, one or more registration points102 may be used to facilitate alignment of cover 372, spacer layer 364,and/or base layer 318. Further, portions of the upper surface of spacerlayer 364 can also be coated with an adhesive in order to provideadhesive layer 378 to adhere to cover 372. It is also contemplated thatcover 372 can include adhesive layer 378 (not shown) configured toadhere to spacer layer 364. Following attachment of cover 372,individual test strips 310 may be separated from the laminated reel. Inan exemplary embodiment, the separation process may include stamping or“punching out” individual test strips 310 in a singulation process.

Preferred embodiments of the present invention have been describedabove. Those skilled in the art will understand, however, that changesand modifications may be made to these embodiments without departingfrom the true scope and spirit of the invention, which is defined by theclaims.

1. A method for manufacturing a biosensor, comprising: positioning ashadow mask containing a pattern of a plurality of feature sets over asubstantially planar base layer containing a plurality of registrationpoints; forming at least one of the plurality of feature sets on thesubstantially planar base layer by selectively depositing a layer of aconductive material on the substantially planar base layer by passingthe conductive material through the pattern of the shadow mask; andremoving the shadow mask from the substantially planar base layer. 2.The method of claim 1, wherein the shadow mask includes at least one ofmolybdenum, aluminum, nickel, silicon, and a polymer.
 3. The method ofclaim 2, wherein the polymer includes polyethylene terephthalate.
 4. Themethod of claim 1, wherein at least one of the plurality of feature setsincludes at least one of a working electrode, a counter electrode, afill-detect electrode, an auto-on conductor, and a coding region.
 5. Themethod of claim 1, wherein the plurality of registration points areformed by at least one of laser ablation, etching, drilling, printing,punching, scoring, heating, compression, and molding.
 6. The method ofclaim 1, wherein the plurality of feature sets formed on thesubstantially planar base layer are separated by less than 10 mm.
 7. Themethod of claim 1, wherein the plurality of registration points areseparated by less than 500 mm.
 8. The method of claim 1, wherein theplurality of feature sets formed on the substantially planar base layerare formed at a density greater than one per 400 mm².
 9. The method ofclaim 1, wherein the plurality of feature sets formed on thesubstantially planar base layer are formed at a density greater than adensity of the plurality of registration points on the substantiallyplanar base layer.
 10. The method of claim 1, wherein at least one ofthe plurality of feature sets is less than 40 mm in length.
 11. Themethod of claim 1, wherein at least one of the plurality of registrationpoints is less than 10 mm wide.
 12. The method of claim 1, whereinpositioning the shadow mask over the substantially planar base layerfurther includes using an adhesive material to at least partiallymaintain the position of the shadow mask over the substantially planarbase layer.
 13. The method of claim 12, wherein the adhesive materialincludes at least one of a pressure sensitive adhesive and a heatactivated adhesive.
 14. The method of claim 1, wherein depositing thelayer of the conductive material includes at least one of physical vapordeposition, electroplating, ultrasonic spraying, and pressure spraying.15. The method of claim 14, wherein physical vapor deposition includesat least one of sputtering and evaporation.
 16. The method of claim 1,wherein the conductive material includes at least one material selectedfrom the group consisting of palladium, gold, platinum, silver, iridium,carbon, indium tin oxide, indium zinc oxide, copper, aluminum, gallium,iron, mercury amalgams, tantalum, titanium, zirconium, nickel, osmium,rhenium, rhodium palladium, an organometallic, and a metallic alloy. 17.The method of claim 1, wherein the method further includes depositing abonding layer on the substantially planar base layer before depositingthe conductive material on the substantially planar base layer.
 18. Themethod of claim 17, wherein the bonding layer includes at least one oftitanium and chromium.
 19. The method of claim 1, wherein the methodfurther includes depositing a reagent layer to contact a portion of theplurality of feature sets.
 20. The method of claim 19, wherein thereagent layer further includes at least one of glucose oxidase, glucosedehydrogenase, potassium ferricyanide, and ruthenium hexamine. 21-39.(canceled)
 40. A biosensor, comprising: a substantially planar baselayer; and a plurality of conductive components formed on thesubstantially planar base layer, wherein at least one of the pluralityof conductive components includes a wall feature.
 41. The biosensor ofclaim 40, wherein the plurality of conductive components includes atleast one of a working electrode, a counter electrode, a fill-detectanode, a fill-detect cathode, an auto-on conductor, and a coding region.42. The biosensor of claim 40, wherein the plurality of conductivecomponents includes at least one material selected from the groupconsisting of gold, platinum, silver, iridium, carbon, indium tin oxide,indium zinc oxide, copper, aluminum, gallium, iron, mercury amalgams,tantalum, titanium, zirconium, nickel, osmium, rhenium, rhodium,palladium, an organometallic, and a metallic alloy.
 43. The biosensor ofclaim 40, wherein the plurality of conductive components are separatedby less than 10 mm.
 44. The biosensor of claim 40, wherein the pluralityof conductive components formed on the substantially planar base layerare formed by at least one of physical vapor deposition, electroplating,ultrasonic spraying and pressure spraying.
 45. The biosensor of claim44, wherein physical vapor deposition includes at least one ofsputtering and evaporation.
 46. The biosensor of claim 40, wherein thewall feature includes as least one of an intrusion and a protrusion. 47.The biosensor of claim 40, wherein the wall feature is formed using atleast one of lift-off lithography and a shadow mask.
 48. The biosensorof claim 40, wherein the biosensor further includes a reagent layer tocontact a portion of the plurality of conductive components.
 49. Thebiosensor of claim 48, wherein the reagent layer further includes atleast one of glucose oxidase, glucose dehydrogenase, potassiumferricyanide, and ruthenium hexamine.
 50. The biosensor of claim 40,wherein the biosensor further includes a bonding layer between thesubstantially planar base layer and at least one of the plurality ofconductive components.
 51. The biosensor of claim 50, wherein thebonding layer includes at least one of titanium and chromium.
 52. Thebiosensor of claim 40, wherein at least one of the plurality ofconductive components is less than 40 mm in length.
 53. A reel,comprising: a substantially planar base layer; a plurality ofregistration points formed on the substantially planar base layer; and aplurality of conductive components formed on the substantially planarbase layer, wherein at least one of the plurality of conductivecomponents includes a wall feature.
 54. The reel of claim 53, whereinthe plurality of conductive components includes at least one of aworking electrode, a counter electrode, a fill-detect anode, afill-detect cathode, an auto-on conductor, and a coding region.
 55. Thereel of claim 53, wherein the plurality of conductive componentsincludes at least one material selected from the group consisting ofgold, platinum, silver, iridium, carbon, indium tin oxide, indium zincoxide, copper, aluminum, gallium, iron, mercury amalgams, tantalum,titanium, zirconium, nickel, osmium, rhenium, rhodium, palladium, anorganometallic, and a metallic alloy.
 56. The reel of claim 53, whereinthe plurality of conductive components are separated by less than 10 mm.57. The reel of claim 53, wherein the plurality of conductive componentsformed on the substantially planar base layer are formed by at least oneof physical vapor deposition, electroplating, ultrasonic spraying andpressure spraying.
 58. The reel of claim 57, wherein physical vapordeposition includes at least one of sputtering and evaporation.
 59. Thereel of claim 53, wherein the wall feature includes as least one of anintrusion and a protrusion.
 60. The reel of claim 53, wherein the wallfeature is formed using at least one of lift-off lithography and ashadow mask.
 61. The reel of claim 53, wherein the reel further includesa bonding layer between the substantially planar base layer and at leastone of the plurality of conductive components.
 62. The reel of claim 61,wherein the bonding layer includes at least one of titanium andchromium.
 63. The reel of claim 53, wherein the biosensor furtherincludes a reagent layer to contact a portion of the plurality ofconductive components.
 64. The reel of claim 63, wherein the reagentlayer further includes at least one of glucose oxidase, glucosedehydrogenase, potassium ferricyanide, and ruthenium hexamine.
 65. Thereel of claim 53, wherein the plurality of registration points areformed by at least one of laser ablation, etching, drilling, printing,punching, scoring, heating, compression and molding.
 66. The reel ofclaim 53, wherein the plurality of registration points are separated byless than 500 mm.
 67. The reel of claim 53, wherein the plurality ofconductive components formed on the substantially planar base layer areformed at a density greater than a density of the plurality ofregistration points formed on the substantially planar base layer. 68.The reel of claim 53, wherein at least one of the plurality ofconductive components is less than 40 mm in length.
 69. The reel ofclaim 53, wherein at least one of the plurality of registration pointsis less than 10 mm wide.